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De novo and acquired resistance to the anti-tumour drug gefitinib (ZD1839; Iressa), a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) has been reported. We have determined whether signalling through the IGF-I receptor (IGF-1R) pathway plays a role in the gefitinib-acquired resistance phenotype. Continuous exposure of EGFR-positive MCF-7-derived tamoxifen resistant breast cancer cells (TAM-R) to 1 mM gefitinib resulted in a sustained growth inhibition (90%) for 4 months before the surviving cells resumed proliferation. A stable gefitinibresistant subline (TAM/TKI-R) was established after a further 2 months and this showed no detectable basal phosphorylated EGFR activity. Compared with the parental TAM-R cells, the TAM/ TKI-R cells demonstrated (a) elevated levels of activated IGF-1R, AKT and protein kinase C (PKC)d, (b) an increased sensitivity to growth inhibition by the IGF-1R TKI AG1024 and (c) an increased migratory capacity that was reduced by AG1024 treatment. Similarly, the EGFR-positive androgen-independent human prostate cancer cell line DU145 was also continuously challenged with 1 mM gefitinib and, although substantial growth inhibition (60%) was seen initially, a gefitinibresistant variant (DU145/TKI-R) developed after 3 months. Like their breast cancer counterparts, the DU145/TKI-R cells showed increases in the levels of components of the IGF-1R signalling pathway and an elevated sensitivity to growth inhibition by AG1024 compared with the parent DU145 cell line. Additionally, DU145/TKI-R cell migration was also decreased by this inhibitor. We have therefore concluded that in breast and prostate cancer cells acquired resistance to gefitinib is associated with increased signalling via the IGF-1R pathway, which also plays a role in the invasive capacity of the gefitinib-resistant phenotype.

Reading the same storybooks repeatedly helps preschool children learn words. In addition, sleeping shortly after learning also facilitates memory consolidation and aids learning in older children and adults. The current study explored how sleep promotes word learning in preschool children using a shared storybook reading task. Children were either read the same story repeatedly or different stories and either napped after the stories or remained awake. Children's word retention were tested 2.5 h later, 24 h later, and 7 days later. Results demonstrate strong, persistent effects for both repeated readings and sleep consolidation on young children's word learning. A key finding is that children who read different stories before napping learned words as well as children who had the advantage of hearing the same story. In contrast, children who read different stories and remained awake never caught up to their peers on later word learning tests. Implications for educational practices are discussed.

Results. On average, there was a large improvement in WOMAC scores 12 months after surgery, but whereas some patients improved, others got worse. The OMERACT-OARSI method classified 85.7% of patients as responders, MID 70.1%, and return to normal 64.1%. In general, each approach classified the same groups of patients as responding to THR. Based on total WOMAC score, patients who were younger, morbidly obese, employed, and better educated were more likely to respond to THR, but the effects were attenuated after adjustment for confounding, with only the effect of education remaining important. Conclusion. The overall average response to THR was good, but ϳ14 -36% of patients did not improve, or were worse, 12 months postsurgery. Although the OMERACT-OARSI criteria were originally designed for use in clinical drug trials, they performed well in classifying patient response 12 months post-THR. Further research is required to understand the determinants of patient outcomes following THR.

Adults with haemophilia and other bleeding disorders often develop lower limb musculoskeletal problems associated with bleeds into joints and muscles, which may affect balance performance and increase likelihood of falling. The aim of this study was to evaluate the effectiveness of an individualized balance and strength home exercise programme on improving balance and related outcomes for adults with haemophilia and other bleeding disorders. Twenty male adults with haemophilia and other bleeding disorders (mean age 39.4 years, 95% CI = 33.7-45.1) were recruited to participate. They underwent a comprehensive clinical and force platform assessment of balance and related measures. Based on assessment findings, the assessing physiotherapist provided an individualized home exercise programme of balance, strengthening and walking exercises. Re-assessment occurred after the 4-month exercise programme. Twelve participants (60%) completed the programme and were re-assessed. There were no safety problems or dropouts associated with the exercise programme aggravating joint status. Although there were no statistically significant changes in any of the measures (adjusted for multiple comparisons), there were improvements of between 5% and 22% on 10 of the 16 measures, with the Neurocom modified Clinical Test of Sensory Interaction on Balance (P = 0.036) and Timed Sit to Stand (P = 0.064) approaching significance. A tailored home exercise programme targeting balance, strengthening and walking is feasible for adults with haemophilia and other bleeding disorders. These results suggest that positive physical outcomes including improved balance and mobility may be achieved with this type of programme.

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Background Currently, over 300 languages are spoken in Australian homes. People without proficient English from non-English speaking countries may not receive equitable care if their health care workers do not speak their primary language. Use of professional interpreters is considered the gold standard; however, for a variety of reasons, it is often limited to key aspects of care such as diagnosis and consent. With the emergence of mobile technologies, health care workers are increasingly using digital translation tools to fill this gap. However, many of these technologies have not been developed for health care settings and their use has not been evaluated. Objective This study aimed to evaluate iPad-compatible language translation apps to determine their suitability for enabling everyday conversations in health care settings. Methods Translation apps were identified by searching the Apple iTunes Store and published and grey literature. Criteria for inclusion were that the apps were available at no cost, able to translate at least one of the top 10 languages spoken in Australia, and available for use on iPad. Apps that met inclusion criteria were reviewed in 2 stages. Stage 1 was the feature analysis conducted by 2 independent researchers, where apps were evaluated for offline use, input and output methods, and number of languages. Stage 2 was the analysis of suitability for everyday communication in the health care setting, conducted by 2 independent professionals with expertise in translation and cross-cultural communication. Apps that enabled key aspects of care normally within the realm of professional interpreters, such as assessment, treatment and discharge planning, and seeking consent for medical treatments, were considered unsuitable. Results In total, 15 apps were evaluated. Of these, 8 apps contained voice-to-voice and voice-to-text translation options. In addition, 6 apps were restricted to using preset health phrases, whereas 1 app used a combination of free input and preset phrases. However, 5 apps were excluded before stage 2. In addition, 6 of the 10 remaining apps reviewed in stage 2 were specifically designed for health care translation purposes. Of these, 2 apps were rated as suitable for everyday communication in the health care setting—culturally and linguistically diverse Assist and Talk To Me. Both apps contained simple and appropriate preset health phrases and did not contain conversations that are normally within the realm of professional interpreters. Conclusions All iPad-compatible translation apps require a degree of caution and consideration when used in health care settings, and none should replace professional interpreters. However, some apps may be suitable for everyday conversations, such as those that enable preset phrases to be translated on subject matters that do not require a professional interpreter. Further research into the use of translati...

BackgroundPreventive health care is an important part of general practice however uptake of activities by patients is variable. Monetary incentives for doctors have been used in the UK and Australia to improve rates of screening and immunisation. Few studies have focussed on incentives for patients to attend preventive health care examinations. Our objective was to investigate the use of a monetary incentive to increase patient attendance with their general practitioner for a cardiovascular risk assessment (CVRA).MethodsA pragmatic RCT was conducted in two Australian general practices. Participating GPs underwent academic detailing for cardiovascular risk assessment. 301 patients aged 40–74, who did not have cardiovascular disease, were independently randomised to receive a letter inviting them to a no cost cardiovascular risk assessment with their GP, or the same letter plus an offer of a $25 shopping voucher if they attended. An audit of patient medical records was also undertaken and a patient questionnaire administered to a sub sample of participants. Our main outcome measure was attendance for cardiovascular risk assessment.ResultsIn the RCT, 56/301(18.6%) patients attended for cardiovascular risk assessment, 29/182 (15.9%) in the control group and 27/119 (22.7%) in the intervention group. The estimated difference of 6.8% (95% CI: -2.5% to 16.0%) was not statistically significant, P = 0.15. The audit showed that GPs may underestimate patients’ absolute cardiovascular risk and the questionnaire that mailed invitations from GPs for a CVRA may encourage patients to attend.ConclusionsA small monetary incentive does not improve attendance for cardiovascular risk assessment. Further research should be undertaken to determine if there are other incentives that may increase attendance for preventive activities in the general practice setting.Clinical trials registrationACTRN12608000183381